Deep Vein Thrombosis Resolution Is Modulated by Monocyte CXCR2-Mediated Activity in a Mouse Model
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Jg. 24 (2004-06-01), S. 1130-1137
Online
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Zugriff:
Objective—To determine the role of CXCR2, the receptor for cysteine-X-cysteine (CXC) chemokines, and its primary effector cell, the neutrophil (PMN), on deep venous thrombosis (DVT) resolution.Methods and Results—DVT in BALB/c, anti-CXCR2 antibody-treated, and BALB/c CXCR2−/−mice were created by infrarenal inferior vena cava (IVC) ligation and the thrombus harvested at various time points over 21 days. The CXCR2−/−mice had significantly larger thrombi at early time points (days 2 to 8), and significantly decreased intrathrombus PMNs, monocytes, and neovascularization as compared with controls. Thrombus KC/CXCL1 was significantly higher at 2 days in CXCR2−/−thrombi as measured by enzyme-linked immunosorbent assay. Fibrin content was significantly higher, with less uPA gene expression at 4 days in CXCR2−/−thrombi. Late fibrotic maturation of the thrombus was delayed in the CXCR2−/−mice, with significantly decreased 8 day MMP-2 activity, whereas MMP-9 activity was elevated as compared with controls. Similar impairment in DVT resolution was found at 8 days with anti-CXCR2 inhibition. However, systemic neutropenia, unlike CXCR2 deletion, did not increase the thrombus size as compared with controls.Conclusions—Normal DVT resolution involves CXCR2-mediated neovascularization, collagen turnover, and fibrinolysis, and it is probably primarily monocyte-dependent.
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Deep Vein Thrombosis Resolution Is Modulated by Monocyte CXCR2-Mediated Activity in a Mouse Model
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Autor/in / Beteiligte Person: | De, Sumit K. ; Upchurch, Gilbert R. ; Arenberg, Douglas A. ; Kunkel, Steven L. ; Varga, Andrea ; C. Barry Deatrick ; Henke, Peter K. ; Thanaporn, Porama ; Sukheepod, Pasu ; Wakefield, Thomas W. ; Eliason, J.L. |
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Zeitschrift: | Arteriosclerosis, Thrombosis, and Vascular Biology, Jg. 24 (2004-06-01), S. 1130-1137 |
Veröffentlichung: | Ovid Technologies (Wolters Kluwer Health), 2004 |
Medientyp: | unknown |
ISSN: | 1524-4636 (print) ; 1079-5642 (print) |
DOI: | 10.1161/01.atv.0000129537.72553.73 |
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